PROJECT SUMMARY/ABSTRACT One in five stroke survivors in the United States live with chronic aphasia, a persistent loss of language. Most people with aphasia also have difficulty reading, but the cognitive and neural bases for co-morbid deficits in reading and language are not fully understood. Loss of reading ability, or alexia, causes significant difficulty in activities of daily living. Reading is a recent cultural acquisition in evolutionary time, and children require years of schooling to develop literacy. Thus, normal reading is thought to be parasitic on more general cognitive and neural systems. Parallel to healthy reading, alexia is hypothesized to reflect insult to more general cognitive and neural systems. Despite this proposition, how language deficits in stroke translate to non-visual reading deficits is underspecified. Moreover, despite strong evidence that white matter disconnections are crucial determiners of language outcomes in chronic stroke, the role of structural disconnections in alexia is not known. This lesion study aims to dissect component cognitive systems and brain connections critical for reading. Normally, reading involves a cooperative division of labor between phonological and semantic processes. Acquired deficits in these reading processes manifest as difficulty reading specific word types. Particularly, effects of lexicality (word vs. pseudoword), orthographic regularity (regular vs. irregular spelling-sound mappings), and imageability (poor vs. rich mental imagery) define phonological and semantic reading deficits. Preliminary cortical lesion-symptom mapping and behavioral data from a previously collected group of chronic stroke survivors suggest that specific word types are differentially dependent on phonological and semantic subprocesses, including articulatory coding, auditory-motor integration, and executive control over semantic representations. This previous study?s abridged reading battery and lack of structural connectome data limited the behavioral relationships we were able to observe, and precluded measurement of key white matter pathways. This prospective study of chronic left hemisphere stroke will identify the cognitive deficits (Aim 1) and structural disconnections (Aim 2) underlying alexia through integration of rigorous behavioral testing with structural connectome-symptom mapping (NIDCD Voice, Speech, and Language Program: Language & Literacy mission areas). The main hypothesis is that post-stroke effects of lexicality, regularity, and imageability on reading relate differentially to deficits in phonological and semantic subprocesses. Generalized linear mixed modeling will determine associations between behavioral measures of articulatory coding, auditory-motor integration, semantic control, and semantic representation with reading deficits along the axes of lexicality, regularity, and imageability. Structural connectome-symptom mapping will determine disconnections associated with reading deficits along these axes and the anatomical basis for convergence between language and reading deficits identified in behavioral analyses. This study will elucidate the insults to cognition and brain structure that underlie reading deficits in stroke, which can guide predictions of post-stroke reading and language outcomes.